A021101 Pre-activation Date: March 15, 2013 ALLIANCE FOR CLINICAL TRIALS IN ONCOLOGY ALLIANCE A021101 NEOADJUVANT FOLFIRINOX AND CHEMORADIATION FOLLOWED BY DEFINITIVE SURGERY AND POSTOPERATIVE GEMCITABINE FOR PATIENTS WITH BORDERLINE RESECTABLE PANCREATIC ADENOCARCINOMA: AN INTERGROUP SINGLE-ARM PILOT STUDY An Alliance trial conducted by CALGB*, NCCTG, and ACOSOG Commercial agent(s): mFOLFIRINOX, capecitabine, gemcitabine Limited Access Study Study Chair Surgical Co-chair Matthew HG Katz, MD Syed Ahmad, MD UT MD Anderson Cancer Ctr University of Cincinnati Houston, TX Tel: 513-584-8900 Tel: 713-794-4660 [email protected] Fax: 713-794-1252 [email protected] Medical Oncology Co-chair Radiation Oncology Study Co-chair Correlative Science Co-chair Robert Marsh, MD Joseph Herman, MD Eric Collisson, MD NorthShore University Johns Hopkins Hospital Univ. of California, San Fran. Tel: 847-570-2515 Tel: 410-502-3823 Tel: 415-476-0624 [email protected] [email protected] [email protected] Imaging Co-Chair GI Committee Chair Pathology Co-chair Lawrence Schwartz, MD Alan P. Venook, MD Wendy Frankel, MD Univ. of California San Fran. Univ. of California, San Fran. The Ohio State University Tel: 415-476-0624 Tel: 415-353-9888 Tel: 614-293-7625 Lawrence Schwartz [email protected] [email protected] [email protected] Primary Statistician Protocol Coordinator Qian Shi, PhD Colleen Watt Mayo Clinic Alliance Central Office Tel: 507-538-4340 Tel: 773-702-4670 [email protected] [email protected] Participating Institutions John Hopkins University Hospital (ECOG, RTOG); University of Chicago (CALGB, ACOSOG, RTOG); MD Anderson Cancer Center (CALGB, ACOSOG); University of Cincinatti (NCCTG, ACOSOG, SWOG); NorthShore University Health System (CALGB, ACOSOG, ECOG, RTOG); University of Louisville (ACOSOG, RTOG SWOG); Oschner Medical Center (ECOG, NCCTG, RTOG); University of Wisconsin (ACOSOG, ECOG, RTOG); The Ohio State University (CALGB, RTOG); Vanderbilt University (ACOSOG, ECOG); University of California San Diego (CALGB, ACOSOG, RTOG); Wake Forest (CALGB, ACOSOG); University of California San Francisco (CALGB, ACOSOG, RTOG) For NCI Use Only 1 Version Date: 2/12/13 03/15/13 Downloaded From: https://jamanetwork.com/ on 09/27/2021 A021101 Alliance Central Protocol Operations Office Alliance Statistical Data Center 230 West Monroe Street, Suite 2050 Mayo Clinic Chicago, IL 60606 200 First St. SW Tel: 773-702-9171 Fax: 312-345-0117 Rochester MN 55905 www.alliance-website.org Expedited Adverse Event Reporting Medidata Rave® iMedidata portal http://ctep.cancer.gov/reporting/adeers.html https://login.imedidata.com OPEN (Oncology Patient Enrollment Network) https://open.ctsu.org Protocol Resources: A021101 Data Manager: Nina Schneider Tel: 507-538-3829 Email: [email protected] A021101 Nursing Contact A021101 Pharmacy Contact Name: Nancy Vaught, RN, OCN Name: Brenda K. Gebhart, RPh Institution: Upstate Carolina CCOP Institution: Missouri Baptist Medical Center Tel: 864-560-7579 E-mail: [email protected] Email: [email protected] Alliance Pathology Coordinating Office Alliance Imaging Core Lab The Ohio State University The Ohio State University Innovation Centre Wright Center of Innovation 2001 Polaris Parkway 395 W. 12th Ave., RM #414 Columbus, OH 43240 Columbus, OH 43240 Tel: 614-293-7073 Fax: 614-293-7967 Tel: 614-293-9151 Fax: 614-293-9275 [email protected] [email protected] Protocol-related questions may be directed as follows: Questions Contact (via email) Questions regarding patient eligibility, treatment, and Study Chair, Nursing Contact, Protocol Coordinator, dose modification: or (where available) Data Manager Questions related to data submission or patient Data Manager follow-up: Questions regarding the protocol document: Protocol Coordinator Questions related to IRB issues and model consent Regulatory Affairs Manager: [email protected] revisions: Questions regarding AdEERS reporting: Linda Bressler, PharmD: [email protected] 2 03/15/13 Downloaded From: https://jamanetwork.com/ on 09/27/2021 A021101 CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION To submit site registration For patient enrollments: Submit study data directly to the documents: NCCTG/Alliance: CTSU Regulatory Office Please refer to the patient Research Base Operations 1818 Market Street, Suite enrollment section for Quality Assurance Office 1100 instructions on using the NW Clinic 3-24-CC Philadelphia, PA 19103 OPEN system. 200 First Street SW Phone – 1-866-651-CTSU Rochester, MN 55905 Fax – 215-569-0206 Attn: QAS for A021101 Note: NCCTG sites will submit all forms via NCCTG Remote Data Entry System. CALGB and ACOSOG participant sites will submit study data using paper CRF forms and a cover sheet located in the Forms Packet. Do not submit study data or forms to the CTSU Data Operations. Do not copy the CTSU on data submissions. The study protocol and all related forms and documents must be downloaded from the protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org. Sites must use the current form version and adhere to the instructions and submission schedule outlined in the protocol. CTSU sites should follow procedures outlined in the protocol for Site registration, Patient Enrollment, Adverse Event Reporting, Data Submission (including ancillary studies), and Drug Procurement. For patient eligibility or treatment-related questions contact the Study PI of the Coordinating Group. For questions unrelated to patient eligibility, treatment, or data submission contact the CTSU Help Desk by phone or e-mail: CTSU General Information Line – 1-888-823-5923, or [email protected]. All calls and correspondence will be triaged to the appropriate CTSU representative. For detailed information on the regulatory and monitoring procedures for CTSU sites please review the CTSU Regulatory and Monitoring Procedures policy located on the CTSU members’ website https://www.ctsu.org. The CTSU Web site is located at https://www.ctsu.org. The following cooperative groups have formally endorsed this trial. Institutions from these groups must enroll patients and submit data via the CTSU. SWOG ECOG RTOG Syed Ahmad, MD Robert Marsh, MD Joseph Herman, MD Tel: 513-584-8900 Tel: 847-570-2515 Tel: 410-502-3823 [email protected] [email protected] [email protected] 3 03/15/13 Downloaded From: https://jamanetwork.com/ on 09/27/2021 A021101 NEOADJUVANT FOLFIRINOX AND CHEMORADIATION FOLLOWED BY DEFINITIVE SURGERY AND POSTOPERATIVE GEMCITABINE FOR PATIENTS WITH BORDERLINE RESECTABLE PANCREATIC ADENOCARCINOMA: AN INTERGROUP SINGLE-ARM PILOT STUDY Pre-registration Eligibility Criteria Required Pre-registration Lab Values Documentation of Disease: Granulocytes ≥ 2,000 /µl Cytologic or histologic proof of adenocarcinoma of the Hemoglobin > 9 g/dL pancreatic head or uncinate process. Platelets ≥ 100,000/µl Objective radiographic staging Albumin > 3.0 g/dL Borderline resectable primary tumor Creatinine ≤ 1.5 x ULN No potentially resectable disease No metastatic disease No locally advanced and unresectable disease AST/ALT ≤ 2.5 x ULN No prior chemotherapy or chemoradiation for panc cancer No currently active second malignancy other than non-melanoma Required Registration Laboratory Values skin cancer No baseline peripheral sensory neuropathy ≥ grade 2 Bilirubin ≤ 2 mg/dL No known Gilbert’s Syndrome or homozygosity for UGT1A1*2 CA 19-9 < 1000 U/mL (from time No history of pulmonary embolism in past 6 months. point when bilirubin is < 2 Age ≥ 18 years mg/dL) ECOG Performance Status 0-1 Non-pregnant and non-nursing Registration Eligibility Criteria Confirmation of radiographic staging by central reviewers R R P R E E R E R S S E S E T T T - Submit A A G Induction A Combined R image for G G Adjuvant Tx I Therapy G ChemoRT Surgery E Central E E (1 cycle=28days) S (1 cycle=14 days) E Capecitabine w/ Pancreatic- G Review mFOLFIRINOX Gem d 1,8,15 for T RT every day for duodenecto I for 4 cycles 2 cycles E A 28 days A A S my R N N N T D D D E R R R R E E E S S S T T T 4 03/15/13 Downloaded From: https://jamanetwork.com/ on 09/27/2021 A021101 TABLE OF CONTENTS SECTION PAGE 1.0 Introduction ......................................................................................................................................... 8 1.1 Rationale for Approach and Design ................................................................................................ 8 1.2 Trial Importance .............................................................................................................................. 9 1.3 Definition of Borderline Resectable PDAC .................................................................................. 10 1.4 Neoadjuvant Therapy for Borderline Resectable PDAC .............................................................. 11 1.5 Neoadjuvant Therapy for Resectable PDAC ................................................................................ 11 1.6 “Neoadjuvant” Therapy for Locally Advanced PDAC ................................................................. 12 1.7 Palliative Therapy for Locally Advanced PDAC .......................................................................... 12 1.8 FOLFIRINOX for Pancreatic Cancer ........................................................................................... 12 1.9 Postoperative Gemcitabine as Adjuvant Therapy for Resected Pancreatic Cancer ...................... 13 1.10 Correlative Study Rationale and Design ....................................................................................